title: A time to look back: analysis of morphokinetic characteristics of human embryo development.
abstract: OBJECTIVE
  To describe the times associated with the morphological changes that occur in the embryo during preimplantation development based on the largest sample size described with time lapse.
  
  
  METHODS
  Cohort study.
  
  
  METHODS
  University-affiliated private center.
  
  
  METHODS
  A total of 9,530 embryos from 1,806 intracytoplasmic sperm injection (ICSI) cycles.
  
  
  METHODS
  None.
  
  
  METHODS
  Using a time-lapse system, embryo images were acquired for at least 68 hours, in some cases reaching 120-130 hours. Embryo cleavage time points up to 8-cell-stage (t2-t8) as well as morulae (tM) and blastocyst formation (tB) were registered in hours after ICSI. Additionally, duration of the cell cycle (cc) and synchrony (s) of the second and third cell cycles were defined. Finally, four subgroups of embryos were considered: the "regular divisions" group excluded embryos with a direct cleavage from 1 to 3 or 2 to 5 cells, and the "viable 8-cell," the "viable blastocyst," and "implanted embryos" groups included only embryos viable to the 8-cell stage, blastocyst stage, or transferred and successfully implanted, respectively.
  
  
  RESULTS
  Averages of times in the general population were: t2 = 27.9 hours, t3 = 38.2 hours, t4 = 40.7 hours, t5 = 51.0 hours, t6 = 54.1 hours, t7 = 56.7 hours, t8 = 59.1 hours, tM = 86.6 hours, tB = 104.1 hours, cc2 = 10.3 hours, cc3 = 12.8 hours, s2 = 2.7 hours, and s3 = 9.9 hours. Comparison between groups showed significant differences between regular divisions and viable 8 cells for t2, t3, t5, cc2, cc3, s2, and s3; between 8 cells and blastocyst for t5, t8, tM, cc3, and s2; and between blastocyst and implanted embryos for t8, tM, tB, and s2. Differences in timing related to morphology of cleavage- and blastocyst-stage embryos were detected.
  
  
  CONCLUSIONS
  A time-lapse monitoring system applied to embryology allows accuracy and objectivity when defining the basis of embryo development within a clinic. The sample size is the largest ever described that provides consistent information about the normal distribution of embryo developmental timings.
authors.affiliation: Instituto Valenciano de Infertilidad, Universidad de Valencia, Valencia, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Herrero
authors.forename: Alberto
authors.initials: A
authors.lastname: Tejera
authors.forename: Carmela
authors.initials: C
authors.lastname: Albert
authors.forename: Carmina
authors.initials: C
authors.lastname: Vidal
authors.forename: Maria José
authors.initials: MJ
authors.lastname: de los Santos
authors.forename: Marcos
authors.initials: M
authors.lastname: Meseguer
mesh_terms: D001755:Blastocyst / Q000166:cytology* / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology*; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology*; D047108:Embryonic Development / Q000502:physiology*; D006801:Humans; D020554:Sperm Injections, Intracytoplasmic / Q000706:statistics & numerical data*; D059008:Time-Lapse Imaging
keywords: Embryo development; data analysis; morphokinetic; reference embryo cohort; time-lapse